Our goal is to continue to advance the successful, multidisciplinary research agenda of the Antibacterial Resistance Leadership Group (ARLG). In the original award period, the ARLG agenda increased scientific knowledge of antibacterial resistance and sought to mitigate important factors that drive its expansion. We continue to pair an unprecedented team of over two dozen of the world's top investigators with the organizational excellence of the Duke Clinical Research Institute (DCRI), one of the world's largest Academic Research Organizations. Because of the complexity of integrating multiple components of such a large-scale clinical research network, our renewal continues to feature centralized leadership through an Executive Committee and a dual PI approach. One PI (Fowler) focuses primarily on operations and the other (Chambers) focuses largely on scientific agenda. The organizational structure also features Scientific Subcommittees devoted to three priority areas: Gram-negative bacterial infections, Gram-positive bacterial infections, and Diagnostics. These Subcommittees are supported by internationally recognized Collaborating Investigators to advance four core value areas: 1) Scientific Expertise; 2) Innovations; 3) Mentoring and Diversity; and 4) Network Development. To complement the ongoing research activities of both the diagnostic and the pharmaceutical industries, our ARLG has established collaborative ties with members of both communities. Our long-term research goal is to improve outcomes of multiple-drug resistant (MDR) bacterial infections by designing and conducting transformational diagnostic and therapeutic clinical trials. Our research portfolio will pursue this goal in therapeutics by conducting first-in kind strategy trials in MDR Gram-negative bacteria and MRSA and by studying nontraditional therapeutics (monoclonal antibodies and bacteriophages) against MDR Pseudomonas aeruginosa. We will pursue this goal in diagnostics by obtaining FDA approval for a host gene expression-based diagnostic and by evaluating the clinical impact of rapid phenotypic testing in patients with bloodstream infection. Our research agenda reflects a realistic strategy of incremental steps towards complex practice-changing trials. Our Specific Aims are to 1) To maintain a Scientific Leadership Center (SLC) that provides overall scientific and administrative leadership for the network; 2) To maintain a Clinical Operations Center (COC) that provides operational support, management, and oversight for the network?s clinical studies and trials; 3) To maintain a Laboratory Center (LC) that advances the ARLG research agenda by leading the development, implementation, and evaluation of essential laboratory research; and 4): To maintain a Statistics and Data Management Center (SDMC) that advances the ARLG research agenda by providing leadership in biostatistics, study design, analysis, interpretation, and publication of results. By advancing these specific aims, our renewal will build upon the productivity and innovation assembled in our original award to advance the ARLG scientific agenda against one of the leading threats to human health.